Increased extravascular lung water (pulmonary edema) is a common cause of pulmonary insufficiency. The Starling hypothesis identifies the factors which regulate fluid flow across capillaries: the capillary to interstitial hydrostitic pressure gradient, the interstitial to capillary oncotic gradient and two descriptors of capillary membrane function with respect to fluid and protein movement. Abberations in one or more of these may result in increased fluid flux into the interstitium. Our goal is to clarify the factors which contribute to or protect from the development of pulmonary edema. We are currently studying the effect of varying plasma oncotic pressure in normal and increased permeability states upon pulmonary transvascular fluid and protein flux. We propose to further investigate the hemodynamic factor governing lung fluid balance. Specifically, we intend to study the effects of acute and chronic changes in cardiac output and left atrial pressure on pulmonary hemodynamics and transcapillary fluid and protein balance in chronically instrumented unanesthetized sheep. These experiments will be conducted in animals previously prepared for the collection of pulmonary lymph, the measurement of pulmonary artery flow, and the recording of pulmonary arterial, left atrial and aortic pressures. Lymph flows, serum and lymph total proteins and oncotic pressures will be measured while protein flux, oncotic pressure gradient and pulmonary microvascular pressure will be calculated. Multiple indicator dilutions curves will be done to determine 1) pulmonary blood flow, 2) extravascular lung water, and 3) 14C urea permeability surface are a product. At the termination of the experiments the animals will be sacrificed to calculate the bloodless wet/dry ratios. Radiolabeled microspheres will be used in the cardiac output experiments to detect changes in the distribution of pulmonary blood flow. The long term objective of our research is to obtain more complete understanding of those factors governing pulmonary transvascular transport of fluid and protein and especially the interactions of and interrelationships between these forces. In this way, we hope to achieve more efficacious therapy for those patients exhibiting clinically significant alterations of extravascular lung water.